Effects of Transcranial Ultrasound Stimulation on Trigeminal Blink Reflex Excitability

Recent evidence indicates that transcranial ultrasound stimulation (TUS) modulates sensorimotor cortex excitability. However, no study has assessed possible TUS effects on the excitability of deeper brain areas, such as the brainstem. In this study, we investigated whether TUS delivered on the substantia nigra, superior colliculus, and nucleus raphe magnus modulates the excitability of trigeminal blink reflex, a reliable neurophysiological technique to assess brainstem functions in humans. The recovery cycle of the trigeminal blink reflex (interstimulus intervals of 250 and 500 ms) was tested before (T0), and 3 (T1) and 30 min (T2) after TUS. The effects of substantia nigra-TUS, superior colliculus-TUS, nucleus raphe magnus-TUS and sham-TUS were assessed in separate and randomized sessions. In the superior colliculus-TUS session, the conditioned R2 area increased at T1 compared with T0, while T2 and T0 values did not differ. Results were independent of the interstimulus intervals tested and were not related to trigeminal blink reflex baseline (T0) excitability. Conversely, the conditioned R2 area was comparable at T0, T1, and T2 in the nucleus raphe magnus-TUS and substantia nigra-TUS sessions. Our findings demonstrate that the excitability of brainstem circuits, as evaluated by testing the recovery cycle of the trigeminal blink reflex, can be increased by TUS. This result may reflect the modulation of inhibitory interneurons within the superior colliculus.

Contribution of nucleus raphe magnus to thermoregulation

Thermoregulation is the maintenance of the core body temperature. The regulation of body temperature is one of the most important functions of the nervous system. Nucleus raphe magnus, as a central circuit coordinates the homeostatic response and maintains body temperature during environmental temperature challenges and adjusts body temperature during the inflammatory response and behavioral states and in response to decreasing energy homeostasis. Our aim in this review is the understanding of thermoregulation by raphe magnus in mammals. This review summarizes the basic concepts of thermoregulation and subsequently assesses the physiological responses to cold stress, including skin blood flow control, sweating, sympathetic-derived cutaneous vasoconstriction and peripheral thermoregulatory control in brown adipose tissue.

Nociceptive Processing

Chapter 2 describes the molecular events associated with pain signaling. The mechanisms associated with chemical, thermal, and mechanical pain signaling in the peripheral nerve endings are detailed. Molecular signaling mechanisms occurring in the spinal dorsal horn, including the primary afferent nociceptor, the inhibitory interneurons, and the descending on-cells and off-cells projecting from the nucleus raphe magnocellularis are described. Persistent increases in pain signaling resulting from inflammatory mediators are explained with reference to specific molecules. Signaling events at supraspinal levels, such as the thalamus, cortex, periaqueductal gray, and nucleus raphe magnus, including cannabinoids, opioids, and noradrenergic and serotonergic neurotransmitter events, are described as critical to pain pathways with relevance to potential pain therapies.

Altered activity in the nucleus raphe magnus underlies cortical hyperexcitability and facilitates trigeminal nociception in a rat model of medication overuse headache

Background The pathogenesis of medication overuse headache (MOH) involves hyperexcitability of cortical and trigeminal neurons. Derangement of the brainstem modulating system, especially raphe nuclei may contribute to this hyperexcitability. The present study aimed to investigate the involvement of the nucleus raphe magnus (NRM) in the development of cortical and trigeminal hyperexcitability in a rat model of MOH. Results Chronic treatment with acetaminophen increased the frequency of cortical spreading depression (CSD) and the number of c-Fos-immunoreactive (Fos-IR) neurons in the trigeminal nucleus caudalis (TNC). In the control group, muscimol microinjected into the NRM increased significantly the frequency of CSD-evoked direct current shift and Fos-IR neurons in the TNC. This facilitating effect was not found in rats with chronic acetaminophen exposure. In a model of migraine induced by intravenous systemic infusion of nitroglycerin (NTG), rats with chronic exposure to acetaminophen exhibited significantly more frequent neuronal firing in the TNC and greater Fos-IR than those without the acetaminophen treatment. Muscimol microinjection increased neuronal firing in the TNC in control rats, but not in acetaminophen-treated rats. The number of Fos-IR cells in TNC was not changed significantly. Conclusion Chronic exposure to acetaminophen alters the function of the NRM contributing to cortical hyperexcitability and facilitating trigeminal nociception.